beta-carotene and Uterine-Cervical-Neoplasms

Cervix carcinoma is an important health problem world-wide, being the second most common cancer among women, ranking first in many developing countries. A number of important epidemiological risk factors have been identified as contributing to the development of CIN and invasive cervix carcinoma. Of key importance is infection with human papillomavirus (HPV), which is the primary risk factor. There are evolving primary and secondary preventive strategies that could further reduce the burden from cervical carcinoma. The possible primary preventive strategies include risk reduction, diet or dietary supplements, HPV vaccines, and other chemopreventive agents. The possible advances in secondary preventive strategies include new technologies for Pap smears, HPV typing triage, and other adjuvant screening procedures. The impact of these strategies will depend upon evidence to support their use along with the characteristics of the population and environment in which they are used.

Topics: Anticarcinogenic Agents; Antioxidants; Ascorbic Acid; beta Carotene; Carcinoma, Squamous Cell; Clinical Trials as Topic; Colposcopy; Diet; Female; Folic Acid; Humans; Image Processing, Computer-Assisted; Mass Screening; Nutritional Requirements; Papanicolaou Test; Papillomaviridae; Papillomavirus Infections; Photochemotherapy; Risk Factors; Tumor Virus Infections; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms; Vaginal Smears; Viral Vaccines; Vitamin E; Vitamins

Invasive cervical cancer accounts for 11.6% of all cancers worldwide and is the second most common cancer among women. It is the most common cancer among women living in less developed countries. Although infection with oncogenic-type human papillomaviruses (HPV) is associated with most cases of cervical cancer, HPV infection alone is an insufficient cause of cervical cancer. Research from the last two decades suggests a role for nutrients in the prevention of cervical cancer. However, results from phase III folic acid and beta-carotene chemoprevention trials have been negative. Potential reasons for the lack of treatment effect are discussed within the context of cervical carcinogenesis.

Topics: beta Carotene; Dietary Supplements; Female; Folic Acid; Humans; Treatment Outcome; Tretinoin; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms

We review the current status of prevention trials in the management of cervical intraepithelial neoplasia (CIN) and cervical cancer. Two large, randomized controlled trials have shown that folic acid is inactive in reversing low to moderate grade CIN. A large randomized trial of locally applied beta-trans retinoic acid showed that the agent was effective in reversing moderate but not severe CIN. Results from a pilot trial involving 30 patients with CIN I (mild dysplasia) and CIN II (moderate dysplasia) indicate that beta-carotene can suppress CIN; a large ongoing randomized trial will answer the question more definitively.

Topics: Antioxidants; beta Carotene; Carotenoids; Female; Humans; Randomized Controlled Trials as Topic; Tretinoin; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms

The aim of this paper was to evaluate the factors that predict regression of untreated CIN 2 and 3. A total of 93 patients with colposcopic persistent CIN 2 and 3 lesions after biopsy were followed for 6 months. Human papillomavirus (HPV) types were determined by polymerase chain reaction at enrolment. We analysed the biologic and demographic predictors of natural regression using univariate and multivariate methods. The overall regression rate was 52% (48 out of 93), including 58% (22 out of 38) of CIN 2 and 47% (26 out of 55) of CIN 3 lesions (P=0.31 for difference). Human papillomavirus was detected in 84% (78 out of 93) of patients. In univariate analysis, 80% (12 out of 15) of lesions without HPV regressed compared to 46% (36 out of 78) of lesions with HPV infection (P=0.016). Women without HPV and those who had a resolution of HPV had a four-fold higher chance of regression than those with persistent HPV (relative odds=3.5, 95% CI=1.4-8.6). Women with five or fewer lifetime sexual partners had higher rates of regression than women with more than five partners (P=0.003). In multivariate analysis, HPV status and number of sexual partners remained as significant independent predictors of regression. In conclusion, HPV status and number of lifetime sexual partners were strongly predictive of regression of untreated CIN 2 and 3.

Topics: Adolescent; Adult; beta Carotene; Colposcopy; DNA, Viral; Double-Blind Method; Female; Humans; Incidence; Marital Status; Middle Aged; Papillomaviridae; Papillomavirus Infections; Polymerase Chain Reaction; Prospective Studies; Risk Factors; Sexual Partners; Sexually Transmitted Diseases, Viral; Tumor Virus Infections; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms

To evaluate the effect of daily beta-carotene (30 mg) versus placebo over a 2-year period on cervical intraepithelial neoplasia (CIN) 2 and 3 lesions. Human papillomavirus (HPV) typing was done to determine whether lesion regression was related to HPV. Micronutrient levels were measured to determine whether levels were predictive of regression. Variables that influence the risk of HPV infection and CIN, such as cigarette smoking and sexual behavior, were evaluated. Women were randomized to beta-carotene or placebo, with cytology and colposcopy every 3 months. Cervical biopsies were performed before treatment and after 6 and 24 months to evaluate response. Persistence of or progression to CIN 3 resulted in removal from the study, whereas treatment continued for 2 years on all others. The presence and type of HPV was determined by PCR. Response was defined as an improvement in CIN by 2 grades. Mantel-Haenszel chi(2) test was used to analyze response to treatment. Fisher's exact test was used to determine the effect of HPV and CIN grade on response Wilcoxon's rank-sum tests were used to compare micronutrient levels between groups. Twenty-one of 124 enrolled women were not randomized because they either moved, became pregnant, voluntarily withdrew, or the pathological review of their initial cervical biopsies did not confirm CIN 2 or 3. Of the remaining 103 women, 33 experienced lesion regression, 45 had persistent or progressive disease, and 25 women did not complete the study and were considered nonresponders in the final analysis. The overall regression rate (32%) was similar between treatment arms and when stratified for CIN grade. Data on 99 women with HPV typing showed that 77% were HPV-positive and 23% HPV-negative at enrollment. HPV-positive lesions were subdivided into indeterminate-, low-, and high-risk categories; the response rate was highest for women with no HPV detected (61%), lower for indeterminate/low-risk (30%), and lowest for high-risk (18%; P =.001). CIN regression was negatively correlated with retinol levels. In conclusion, beta-carotene does not enhance the regression of high-grade CIN, especially in HPV-positive subjects.

Topics: Administration, Oral; Adolescent; Adult; Antioxidants; beta Carotene; Biopsy, Needle; Dietary Supplements; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Logistic Models; Long-Term Care; Middle Aged; Probability; Reference Values; Severity of Illness Index; Treatment Outcome; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms; Vaginal Smears

A double-blind, placebo-controlled, randomized, factorial study using a daily oral administration of 30 mg beta-carotene and/or 500 mg vitamin C was conducted in 141 women with colposcopically and histologically confirmed minor squamous atypia or cervical intra-epithelial neoplasia (CIN) I. Over approximately 2 years of follow-up, 43 lesions regressed to normal and 13 progressed to CIN II. The regression rate was slightly higher, but not significantly so, in those randomized to beta-carotene compared to no beta-carotene (hazard ratio = 1.58, 95% CI: 0.86-2.93, P = 0.14) and slightly lower, but not statistically significant, for those randomized to vitamin C compared to no vitamin C (hazard ratio = 0.65, 95% CI: 0.35-1.21, P = 0.17). In a model with no interaction, the progression rate was slightly higher in those randomized to beta-carotene (hazard ratio = 1.75, 95% CI: 0.57-5.36, P = 0.32) and also in those randomized to vitamin C (hazard ratio = 2.40, 95% CI: 0.74-7.80, P = 0.13). Neither of these were statistically significant. However, there was some evidence of an interaction effect of the two compounds on the progression rate (P = 0.052), with seven of the progressed lesions occurring in those randomized to both vitamins compared to a total of six in the three other groups. The currently available evidence from this and other trials suggests that high doses of these compounds are unlikely to increase the regression or decrease the progression of minor atypia and CIN I.

Topics: Adult; Antioxidants; Ascorbic Acid; beta Carotene; Disease Progression; Double-Blind Method; Female; Follow-Up Studies; Humans; Precancerous Conditions; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms

The effects of oral supplementation of a 30-mg dose of beta-carotene on the plasma levels of carotenoids, tocopherols, and retinol were studied sequentially in 69 patients participating in a nine-month randomized placebo controlled trial conducted to examine efficacy of beta-carotene to induce regression of cervical intraepithelial neoplasia. At each visit (baseline and 1.5, 3, 6, 9, 10.5, and 15 mo), blood samples were collected and the levels of six micronutrients were determined by high-performance liquid chromatography. No limitations or changes were introduced in each participant's dietary habits. Cervico-vaginal lavage samples were also obtained at the same visit and assayed for the presence of human papillomavirus DNA by Southern blot hybridization and polymerase chain reaction. In the supplemented group, mean plasma beta-carotene levels were significantly higher (p = 0.0001) than baseline and remained markedly elevated for 15 months. In the longitudinal analysis of the placebo group, there were no variations among individual mean plasma levels of beta-carotene, alpha-carotene, lycopene, retinol, gamma-tocopherol, or alpha-tocopherol, suggesting absence of seasonal or dietary changes. In the placebo group, cigarette smoking and steroid contraceptive use were significantly associated with low levels of plasma beta-carotene (p = 0.05 and p = 0.012, respectively). However, in contrast, in the beta-carotene-supplemented group, steroid contraceptive use had no influence on the plasma beta-carotene levels. An additional noteworthy finding was that beta-carotene supplementation did not reverse the depletion effect in smokers. There was no association between the plasma levels of these six micronutrients in women with cervical intraepithelial neoplasia and persistent human papillomavirus infection status in the placebo or the supplemented groups. Functional sequential nutrient interactions with each other or with other essential micronutrients and possible long-term toxicity need to be addressed in clinical trials.

Topics: Adult; beta Carotene; Blotting, Southern; Carotenoids; Contraceptives, Oral, Hormonal; DNA, Viral; Female; Humans; Lycopene; Papillomaviridae; Placebos; Polymerase Chain Reaction; Precancerous Conditions; Smoking; Uterine Cervical Neoplasms; Vitamin A; Vitamin E

Women with histopathologically confirmed cervical intraepithelial neoplasia (CIN) were followed at 3-month intervals in a randomized double-blinded trial to evaluate the efficacy of beta-carotene to cause regression of CIN. Questionnaire data, plasma levels of micronutrients, and a cervicovaginal lavage for human papillomavirus (HPV) detection were obtained at each visit, and an endpoint biopsy was performed at 9 months. Sixty-nine subjects had a biopsy endpoint evaluation; 9 of 39 (23%) subjects in the beta-carotene group versus 14 of 30 (47%) in the placebo group had regression of CIN (P = 0.039). Independent risk factors for persistent CIN at 9 months included type-specific persistent HPV infection (OR = 11.38, P = 0.006) and continual HPV infection with a high viral load (OR = 14.25, P = 0.007) at baseline and 9 months, an initial diagnosis of > or =CIN II (OR = 6.74, P = 0.016), and older age (OR for > or =25 years = 4.10, P = 0.072). After controlling for these factors, the beta-carotene and placebo groups did not differ in risk for having CIN at 9 months (OR = 1.53, P = 0.550). Resolution of baseline HPV infection was significantly correlated with non-high-risk HPV types (RR = 2.94, P = 0.015), age <25 years (RR = 2.62, P = 0.014), and douching after sexual intercourse (RR = 3.02, P = 0.012), but not with randomization group. Our data indicate that a large proportion of mild CIN lesions regress; age and HPV infection play an important role in the natural course of CIN; and repeated HPV testing may have a value in distinguishing women who need aggressive treatment for CIN versus those who do not. Supplementation of beta-carotene does not appear to have a detectable benefit in treatment of CIN.

Topics: Adult; beta Carotene; Double-Blind Method; Female; Humans; Logistic Models; Longitudinal Studies; Multivariate Analysis; Odds Ratio; Papillomaviridae; Papillomavirus Infections; Treatment Outcome; Tumor Virus Infections; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms

Topics: beta Carotene; Biopsy; Cervix Uteri; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Neoplasm Staging; Treatment Outcome; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms

To evaluate the serial changes in colposcopic and cervicographic findings of women with cervical intraepithelial neoplasia (CIN) II and III enrolled in a phase III randomized comparison of oral beta carotene and placebo.. All subjects treated with beta carotene or placebo for at least 6 months were included if they met the criteria of persistent or progressive disease (no change or worsening of CIN grade) or disease regression (improvement of two grades or more). These two groups were compared for changes in colposcopic and cervicographic patterns. Colposcopically directed biopsies and cervicography were done at enrollment and after 6 months. Quarterly Papanicolaou smears and colposcopic assessments also were performed. Findings of mosaic pattern, punctation, and white epithelium were graded and diagrammed at colposcopic examinations. Cervicographic measurements of the centripetal movement of metaplastic epithelium were recorded. Data were analyzed by chi 2 analysis and Fisher exact tests.. Data were available for 23 subjects with regression and 16 with persistent lesions. Small lesions were significantly more likely to regress than large ones. Lesions without coarse punctation were significantly more likely to regress than lesions with coarse punctation, and lesions with mild acetowhite changes were more likely to regress than those with dense white epithelium. A pattern of centripetal movement of the metaplastic epithelium toward the cervical os was noted in lesions that regressed, but not in those that persisted or progressed.. This study describes the centripetal growth of metaplastic squamous epithelium associated with the regression of CIN II and III. This observation contributes to our understanding of the process of disease regression in CIN and may be useful in identifying individuals for conservative management. Failure to identify this pattern correlates with persistent or progressive disease.

Topics: Adult; Antioxidants; beta Carotene; Clinical Trials, Phase III as Topic; Colposcopy; Female; Humans; Middle Aged; Randomized Controlled Trials as Topic; Remission Induction; Retrospective Studies; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms

Transforming growth factor (TGF) beta1 is a potent growth inhibitor of epithelial cells. Loss of responsiveness to TGF-beta1 and/or loss of TGF-beta1 itself may be important in the progression of cervical intraepithelial neoplasia to invasive cervical cancer. Retinoids have antiproliferative effects on epithelial cells and have been used as chemopreventive and chemotherapeutic agents for several human cancers. There is evidence that retinoids exert their effects by promoting the induction of TGF-beta. The aim of this study was to determine whether the expression of TGF-beta1 was altered in patients enrolled in a clinical trial designed to test the therapeutic efficacy of beta-carotene, a carotenoid metabolized to retinol, in cervical intraepithelial neoplasia. Using an immunohistochemical technique, tissues were stained with two types of antisera that react with the intracellular and extracellular forms of TGF-beta1. Matched cervical biopsies taken from 10 patients before and after treatment with beta-carotene were immunostained simultaneously to allow direct comparison of relative staining intensity. A significant increase in intracellular TGF-beta1 immunoreactivity was noted in cervical epithelial cells in patients with cervical intraepithelial neoplasia after treatment with beta-carotene (P = 0.003). These results demonstrate regulation of a TGF-beta isoform in vivo in humans in response to beta-carotene administered as a chemopreventive agent.

Topics: beta Carotene; Chemoprevention; Female; Humans; Immunohistochemistry; Transforming Growth Factor beta; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms

The use of Papanicolaou smears for cervical cancer screening has led to an increased detection of preinvasive conditions of the cervix, cervical intraepithelial neoplasia (CIN). Epidemiological studies have shown an association between low levels of dietary beta-carotene and CIN. In this Phase II study, we have explored the effect of p.o. beta-carotene administration on CIN I and II. Patients with documented CIN I or II were treated with 30 mg daily of beta-carotene for 6 months. Response rates were determined at 0, 3, 6, and 12 months with cytology, colposcopy, and/or biopsies. Levels of beta-carotene and vitamin E were determined at the same time intervals in vaginal mucosa cells and serum. Response rates were 18 of 30 (60%), 21 of 30 (70%), and 10 of 30 (33%) at 3, 6, and 12 months, respectively. Significant changes occurred in the serum beta-carotene levels over time. Median levels over 2200 mg/ml were found at 3 and 6 months versus a baseline median level of 111 (P < 0.0001). Significant increases were also noted in the beta-carotene levels of the vaginal mucosa compared to baseline (P = 0.01) and a significant correlation was noted between serum and vaginal beta-carotene levels as well (P < 0.0001). This study indicates that a large percentage of patients with CIN I and II will respond clinically to p.o. beta-carotene supplementation. There is a positive relationship between serum and tissue levels of beta-carotene which suggests that serum levels can be used for monitoring purposes. Because of these encouraging results, prospective randomized studies are ongoing comparing the efficacy of beta-carotene against an untreated control arm.

Topics: Antioxidants; beta Carotene; Female; Humans; Mucous Membrane; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms; Vagina

The perceived informativeness of a publication can be assessed by measuring the change in belief it induces among the scientific public, regarding a certain hypothesis. In a randomized trial, we studied the effect of empirical evidence from a clinical experiment and a case-control study on the hypothesis that beta-carotene protects against (cervical) cancer. The study population consisted of first authors of recently published patient-oriented research papers. They received an abstract of the clinical experiment, of the case-control study, or a "placebo" abstract. The latter was used to assess the specific effect of the empirical evidence in the two real studies. The change in belief in the hypotheses was expressed as a likelihood ratio (LR). All three abstracts led to a decrease in belief in the hypothesis. The median LRs of the abstracts of the experiment, case-control study and "placebo" were 0.33, 0.45, 0.75 respectively. This paper shows that the belief in a certain hypothesis is influenced by the quality of empirical evidence in a study. The magnitude of change induced by the experimental and case-control abstract had the anticipated order, but the change in belief induced by the "placebo" abstract was larger than we had expected. Reasons for this may be the concise information in the abstract and the variable methodological training of the study population.

Topics: Anticarcinogenic Agents; beta Carotene; Carotenoids; Case-Control Studies; Diffusion of Innovation; Female; Humans; Random Allocation; Statistics as Topic; Surveys and Questionnaires; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms

Some dietary factors could be involved as cofactors in cervical carcinogenesis, but evidence is inconclusive. There are no data about the effect of fruits and vegetables intake (F&V) on cervical cancer from cohort studies. We examined the association between the intake of F&V and selected nutrients and the incidence of carcinoma in situ (CIS) and invasive squamous cervical cancer (ISC) in a prospective study of 299,649 women, participating in the European Prospective Investigation into Cancer and Nutrition study. Cox proportional hazard models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (95% CI). A calibration study was used to control measurement errors in the dietary questionnaire. After a mean of 9 years of follow-up, 253 ISC and 817 CIS cases were diagnosed. In the calibrated model, we observed a statistically significant inverse association of ISC with a daily increase in intake of 100 g of total fruits (HR 0.83; 95% CI 0.72-0.98) and a statistically nonsignificant inverse association with a daily increase in intake of 100 g of total vegetables (HR 0.85: 95% CI 0.65-1.10). Statistically nonsignificant inverse associations were also observed for leafy vegetables, root vegetables, garlic and onions, citrus fruits, vitamin C, vitamin E and retinol for ISC. No association was found regarding beta-carotene, vitamin D and folic acid for ISC. None of the dietary factors examined was associated with CIS. Our study suggests a possible protective role of fruit intake and other dietary factors on ISC that need to be confirmed on a larger number of ISC cases.

Topics: Adult; Aged; Ascorbic Acid; beta Carotene; Carcinoma; Carcinoma, Squamous Cell; Diet; Europe; Female; Folic Acid; Follow-Up Studies; Fruit; Humans; Middle Aged; Neoplasm Invasiveness; Nutrition Surveys; Prospective Studies; Risk Factors; Uterine Cervical Neoplasms; Vegetables; Vitamin A; Vitamin D; Vitamin E

Cervical cancer is one of the most common gynecological malignancies in Korea, although the incidence has been declining in recent years. This study explored whether antioxidant vitamin intakes influenced the risk of cervical cancer. The association between antioxidant vitamin intakes and cervical cancer risk was calculated for 144 cervical cancer cases and 288 age-matched, hospital-based controls using unconditional logistic regression models. Cases reported statistically lower mean dietary intakes of vitamin A, beta -carotene, and vitamin C than did controls. Total intakes of vitamins A and E, which included both dietary and supplement intake, were also lower in cases. Those patients in the highest quartiles of dietary vitamin A, beta -carotene, and vitamin C intakes had statistically significantly lower cervical cancer risks than those in the lowest quartiles for vitamin A, beta -carotene, and vitamin C: odds ratio (OR) = 0.36 [95% confidence interval (CI) = 0.19-0.69), OR = 0.48 (CI = 0.26-0.88), and OR = 0.36 (CI = 0.18-0.69), respectively. Total intakes of vitamins A, C, and E were strongly inversely associated with cervical cancer risk: OR = 0.35 (CI = 0.19-0.65), OR = 0.35 (CI = 0.19-0.66), and OR = 0.53 (CI = 0.28-0.99), respectively. The findings support a role for increased antioxidant vitamin intake in decreasing the risk of cervical cancer. These associations need to be assessed in large prospective studies with long-term follow-up.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; beta Carotene; Case-Control Studies; Diet; Dietary Supplements; Female; Humans; Korea; Logistic Models; Middle Aged; Odds Ratio; Risk Factors; Uterine Cervical Neoplasms; Vitamin A; Vitamin E

Topics: Anticarcinogenic Agents; beta Carotene; Breast Neoplasms; Clinical Trials as Topic; Female; Humans; Lung Neoplasms; Neoplasms; Tamoxifen; Treatment Outcome; Uterine Cervical Neoplasms

The inhibitory effects of the newly-developed forms of beta-carotene--water-soluble and liposomal--have been studied in rats and mice bearing tumors induced in 4 models of carcinogenesis. Mammary tumors were induced by single injections of 1 mg methylnitrosourea into each gland. Esophageal tumors were induced in male rats by intragastric administration of 3 mg/kg methylbenzylnitrosoamine, thrice a week for 4 weeks. Tumors of the vagina and cervix uteri were induced by intravaginal painting with 25 mkg dimethylbenz(a)anthracene, twice a week for 6 weeks. Tumors of the lung were induced in female mice by intraperitoneal injection of 1 g/kg urethane, once a week for 6 weeks. With models I-III, animals received water-soluble beta-carotene (Aquiton-10) with drinking water (200 mg/I), on completion of carcinogen treatment and for another 9-12 months until the end of experiment. Urethane-treated mice received liposomal beta-carotene with drinking water (60 mg/l) 10 days before the beginning of carcinogen treatment and for another 6 months until the end experiment. Water-soluble beta-carotene failed to influence the carcinogenesis in the mammary gland and esophagus in rats; however, it significantly inhibited carcinoma development in murine vagina and cervix uteri (47.0%). Liposomal beta-carotene significantly inhibited lung adenomas (46.4%) and mammary carcinomas (55.6%) in urethane-treated mice.

Topics: Animals; Anticarcinogenic Agents; beta Carotene; Esophageal Neoplasms; Female; Liposomes; Lung Neoplasms; Male; Mammary Neoplasms, Experimental; Mice; Neoplasms, Experimental; Rats; Solubility; Uterine Cervical Neoplasms; Vaginal Neoplasms; Water

The presence of HPV, using the Digene Hybrid Capture System, was identified in a group of 324 women with CIN and in 228 women with normal cytological smears. Risk of occurrence of CIN was 40 times higher for high risk HPV types. The serum folic acid level and the level of antioxidant compounds in plasma (retinol, alpha-tocopherol, vitamins C and E) in women of the studied and control group was determined by HPLC (high-performance liquid chromatography-reversed phase). Statistically lower levels of folic acid were found in the women with CIN-HPV (+) (OR: 7.5: 95% CI: 1.2-9.7). Studies have shown that lower levels of antioxidants coexisting with low levels of folic acid increases the risk of CIN development.

Topics: Antioxidants; beta Carotene; Cocarcinogenesis; Female; Folic Acid; Folic Acid Deficiency; Humans; Papillomaviridae; Papillomavirus Infections; Regression Analysis; Risk Factors; Tumor Virus Infections; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms; Vitamin E

Studies were carried out in 528 women hospitalized in the Department of Obstetrics and Gynecology Medical Academy in Lublin. Besides the control group, patients were classified according to the observed histopathological changes in the cervix (CIN) and found infections with human papillomavirus (HPV). In all cases beta-carotene content in blood serum was examined. HPV infection was probably a cause of decrease of beta-carotene content. It was found that with increased advancement of cervical dysplasia the level of beta-carotene in serum decreased.

Topics: Adolescent; Adult; beta Carotene; Female; Humans; Life Style; Middle Aged; Papillomaviridae; Papillomavirus Infections; Poland; Risk Factors; Smoking; Tumor Virus Infections; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms

Epidemiological studies continue to identify an association of dietary antioxidant micronutrients in cancer prevention. A number of case-control and cohort studies have demonstrated a relationship between high intake of foods rich in carotenoids, tocopherols, and vitamin C with a reduced risk of certain human malignancies. The purpose of this study was to investigate the comparative plasma levels of a profile of known dietary antioxidants, namely, beta-carotene, lycopene, canthaxanthin, retinol, alpha-tocopherol, and tau-tocopherol. The target population was women with a histopathological diagnosis of cervical intraepithelial neoplasia (CIN) or cervical cancer and a control group. All women resided in the same catchment area (Bronx Borough, New York City) and were of similar inner-city socioeconomic backgrounds representing a fairly homogenous population group. A cross-sectional sample of 235 women was recruited with informed consent. Plasma nutrient levels were measured by reverse-phase high pressure liquid chromatography under study codes. The mean plasma levels of carotenoids (beta-carotene, lycopene, and canthaxanthin), as well as alpha-tocopherol, were significantly lower in women with CIN and cervical cancer. In contrast, the mean plasma level of tau-tocopherol was higher among patients with CIN, while the mean plasma level of retinol was comparable among the groups. There were significant linear trends for all three carotenoids and quadratic trends for alpha- and tau-tocopherol with the degree of cervical histopathology. Plasma beta-carotene concentrations in cigarette smokers were significantly lower regardless of cervical pathology, whereas plasma lycopene and canthaxanthin levels were significantly lower in smokers with CIN. The findings of a decrease in all plasma antioxidant nutrient levels except tau-tocopherol in women with CIN and cancer suggest a potential role for antioxidant deficiency in the pathogenesis of CIN and carcinoma of the cervix, which requires further investigation.

Topics: Adult; Aged; beta Carotene; Canthaxanthin; Carotenoids; Chromatography, High Pressure Liquid; Cross-Sectional Studies; Female; Humans; Lycopene; Middle Aged; Smoking; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms; Vitamin A; Vitamin E

We used newly established cervical dysplasia-derived cell lines to elucidate a molecular mechanism of the preventive action of beta-carotene in cervical multi-step carcinogenesis. Liposomal beta-carotene was added to the culture medium for human cervical dysplasia cell lines, CICCN-2 from cervical intraepithelial neoplasia grade I (CIN I), CICCN-3 from CIN II, and CICCN-4 from CIN III, and human cervical carcinoma-derived cell lines such as CICCN-6, CICCN-18, and HeLa cells. beta-Carotene (10 mumol/L) induced significant growth retardation in three cervical dysplasia cell lines but not in three cervical carcinoma-derived cell lines. Binding activities of epidermal growth factor (EGF) and cellular amounts of either messenger RNA for EGF receptor gene or EGF receptor protein were all highest in CICCN-4 cells. Cell surface binding, as well as internalization, of 125I-labeled EGF was rapidly reduced after beta-carotene treatment in dysplasia cell lines and 170-kD protein bands of EGF receptor disappeared from protein immunoblots at day 3 of the treatment. Cellular amounts of EGF receptor messenger RNA remained constant until day 3 of the treatment and were substantially reduced after day 7. Chromatin condensations, morphologic evidence for apoptotic cell death, were observed at day 1 by staining. From these results, we contend that prevention of cervical carcinogenesis by beta-carotene is due to induction of apoptosis in cervical dysplastic cells, which are premalignant cells in cervical multi-step carcinogenesis, via down-regulation of EGF receptor protein.

Topics: Anticarcinogenic Agents; Antioxidants; Apoptosis; beta Carotene; Carotenoids; Down-Regulation; Epidermal Growth Factor; ErbB Receptors; Female; Humans; RNA, Messenger; Tumor Cells, Cultured; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms

We evaluated whether differences in serological nutrient indicators between cases and controls were likely to be due to different usual levels for cases or to altered metabolism due to disease. Blood samples obtained as part of a case-control study of invasive cervical cancer conducted in Latin America were evaluated for case-control differences and for trends with stage of disease. Serum alpha- and beta-carotene, cryptoxanthin, and alpha- and gamma-tocopherol showed no trend with extent of disease, although Stage IV cases had lower alpha- and beta-carotene values than did other cases. A slight trend of decreasing values with stage was observed for serum retinol, lycopene, and lutein. For cholesterol and triglyceride concentrations, an inverse trend was observed with stage of disease, which suggested a clinical effect of the disease on blood lipids. Adjustment for smoking, alcohol intake, or oral contraceptive use did not alter observed relations, nor was there evidence that the altered blood nutrient levels differed by histological type. These data suggest that serum values for some carotenoids from Stage I, II, and III cervical cancer are suitable for etiological studies, but spurious results may be obtained if late-stage cases are included. Evidence of trends with severity of disease for cholesterol and triglycerides, and possibly for retinol, lycopene, and lutein, suggest that special attention be given to disease effects of these nutrients in studies of cervical cancer.

Topics: Adult; beta Carotene; Carotenoids; Cholesterol; Cryptoxanthins; Female; Humans; Latin America; Lutein; Lycopene; Middle Aged; Neoplasm Staging; Nutritional Status; Triglycerides; Uterine Cervical Neoplasms; Vitamin A; Vitamin E; Xanthophylls

The purpose of this study was to measure beta-carotene levels in exfoliated epithelial cervicovaginal cells collected by a lavage technique in normal women and patients with histopathologically diagnosed cervical intraepithelial neoplasia and cervical cancer.. In a cross-sectional sampling of women (n = 105), cervicovaginal cells and plasma beta-carotene levels were assayed with high-pressure liquid chromatography. In addition, beta-carotene levels were measured in exfoliated epithelial samples of cervicovaginal cells obtained from women (n = 24) enrolled in an ongoing oral beta-carotene supplementation clinical trial.. Cervicovaginal cells and plasma beta-carotene levels were found to be significantly decreased in women with cervical intraepithelial neoplasia and cervical cancer as compared with controls (p < 0.0001, analysis of variance). Retinol levels in cervicovaginal cells were undetectable. The beta-carotene levels in cervicovaginal cells were markedly increased in the majority of patients (79%) after oral supplementation as compared with baseline levels in women enrolled in the beta-carotene clinical trial.. The study demonstrates that changes of in situ cellular beta-carotene concentrations are measurable in samples of exfoliated epithelial cells obtained by a noninvasive saline lavage harvesting technique. The current findings further support our previous hypothesis that beta-carotene deficiency may have an etiologic role in the pathogenesis of cervical intraepithelial neoplasia and/or cervical cancer.

Topics: Adolescent; Adult; Aged; beta Carotene; Carotenoids; Cervix Uteri; Female; Humans; Middle Aged; Osmolar Concentration; Therapeutic Irrigation; Tumor Cells, Cultured; Uterine Cervical Neoplasms; Vagina

Chronic human health problems, namely arteriosclerosis, myocardial ischemia, and cancer, may be caused by highly active oxygen species and may be preventable by antioxidant vitamins. In humans, the sources of two major antioxidants, beta-carotene and alpha-tocopherol, are dietary. In this study, we measured the plasma concentrations of beta-carotene and alpha-tocopherol by reverse-phase high-pressure liquid chromatography in a cross-sectional sampling of 116 women. Significantly reduced plasma levels of beta-carotene and alpha-tocopherol were observed in women with histopathologically diagnosed cervical dysplasias or cancer (p less than 0.0001 and p less than 0.005, respectively). There was an inverse association between the plasma levels of both beta-carotene and alpha-tocopherol and increasingly severe graded cervical histopathology. In groups with advanced dysplasias, the percentage of smokers was markedly increased and the women were comparatively older (p less than 0.0001). A strong association was noted between smoking status and plasma beta-carotene levels, independent of cervical pathology. However, this was not evident with respect to alpha-tocopherol. The findings suggest that the antioxidants beta-carotene and alpha-tocopherol have biologic functions that are interdependent in the pathogenesis of cervical intraepithelial lesions and cervical cancer.

Topics: Adolescent; Adult; Age Factors; Analysis of Variance; beta Carotene; Carotenoids; Female; Free Radicals; Humans; Middle Aged; Regression Analysis; Smoking; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms; Vitamin A; Vitamin E

A case-control study examined the association between cervical intra-epithelial neoplasia (CIN) and serum and dietary alpha-carotene, beta-carotene, cryptoxanthin, lutein, and lycopene. Cases (n = 102) had biopsy confirmed CIN I, II or III. Controls matched for age, ethnic origin and clinic (n = 102) had normal Pap smears. Participants completed health history and food frequency questionnaires. Fasting venous blood samples were assayed for serum carotenoids. Multivariable conditional logistic regression analyses yielded odds ratios and 95% confidence intervals (CIs) for those in quartiles 3, 2, and 1 (lowest) compared to quartile 4 (highest) of serum lycopene of 3.5 (1.1-11.5), 4.7 (1.2-17.7) and 3.8 (1.1-12.4), respectively. Similar analyses yielded adjusted odds ratios (ORaS) and 95% CIs of 4.6 (1.1-19.7), 5.8 (1.6-21.3) and 5.4 (1.3-23.3) for dietary intake of lycopene. The findings for lycopene-rich foods (tomatoes) were consistent with this result. CIN was not associated with the lutein. Findings for alpha-carotene, beta-carotene and cryptoxanthin were ambiguous. Quartile of vitamin C intake was also inversely associated with CIN with ORaS and 95% CIs of 3.7 (0.9-14.6), 4.1 (1.0-17.2), and 6.4 (1.4-30.0) for those in quartiles 3, 2, and 1 compared to quartile 4.

Topics: Adult; beta Carotene; Carotenoids; Case-Control Studies; Cryptoxanthins; Diet; Female; Humans; Lutein; Lycopene; Reference Values; Surveys and Questionnaires; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms; Xanthophylls

Topics: beta Carotene; Carotenoids; Female; Humans; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms

The risk of invasive and intraepithelial cervical neoplasia in relation to the frequency of intake of the major sources of preformed vitamin A (retinol) and beta-carotene in the Italian diet was analyzed in a study of 392 cases of invasive cancer compared with 392 age-matched controls hospitalized for acute conditions unrelated to any of the established or suspected risk factors for cervical cancer, and of 247 cases of cervical intraepithelial neoplasia compared with 247 controls found to have normal smears at the same screening clinics where cases had been identified. Women with invasive cancer consumed milk, green vegetables, and carrots less frequently, but no significant relation was noted for meat or liver. Consequently, estimated beta-carotene, but not retinol, intake was inversely and strongly related to the risk of invasive cervical cancer. Compared with women whose intake was over 150,000 international units (IU) per month, the relative risks were 3.0 for 100 to 149,999 and 4.7 for less than 100,000 IU. It was not possible to show that these relationships were incidental, since allowance for several identified potential distorting factors, including indicators of social status and the major risk factors for cervical cancer, did not materially modify the risk estimates. In contrast, no association emerged between any of the food items and vitamin A estimates considered and intraepithelial neoplasia. Thus, the results of this study can be interpreted in one of two ways: either some residual uncontrolled bias was responsible for the strong dietary correlates of invasive cervical cancer risk or beta-carotene (or any other correlate of a vegetable-rich diet) has effect on one of the later stages of the process of carcinogenesis, thus influencing the risk of invasive carcinoma but not of its precursors.

Topics: Adolescent; Adult; Age Factors; Aged; beta Carotene; Carcinoma in Situ; Carotenoids; Diet; Diet Surveys; Female; Humans; Italy; Middle Aged; Risk Factors; Socioeconomic Factors; Uterine Cervical Neoplasms; Vitamin A; Vitamin A Deficiency

Both plasma and dietary measures of vitamin A status were investigated along with previously established risk factors (number of sexual partners, age at first intercourse, smoking, and oral contraceptive use) in a study of 117 in situ cervical cancer patients and 196 matched community controls in Sydney, Australia. Neither total calories nor retinol from foods was related to cancer risk, nor was plasma retinol. When plasma and dietary indexes were considered together, vitamin C, fruit juices, and plasma beta-carotene showed protective effects. Plasma beta-carotene reduced risk from top to bottom quartile by 80%, vitamin C by 60%, and fruit juices by 50%. Thus the evidence suggests that cancer risk is associated with some aspect of diet that is reflected in the effect of plasma beta-carotene. There is no clear effect of any one nutrient but fruit juices appear protective. Thus vitamin C and beta-carotene are likely candidates.

Topics: Adult; Aged; Ascorbic Acid; Australia; beta Carotene; Carcinoma in Situ; Carotenoids; Diet; Female; Humans; Middle Aged; Precancerous Conditions; Uterine Cervical Neoplasms; Vitamin A

The concentrations of retinol and beta carotene were measured in serum samples taken from 113 women with cervical cancer, 32 with invasive and 81 with pre-invasive disease, and compared with those from 226 age-matched control women. There was little difference in serum retinol levels between women with cancer of the cervix, at any stage, and the control women, after adjusting for potential confounding factors. Serum beta carotene concentrations were likewise similar in women with invasive disease and the controls. However mean beta carotene levels were significantly reduced in women with pre-invasive disease compared to the controls (221.3 cf. 291.6 micrograms l-1, P less than 0.05). This reduction was more evident amongst women with a diagnosis of carcinoma-in-situ (mean 213.1 micrograms l-1 than amongst those with severe dysplasia (mean 228.7 micrograms l-1. There is a negative trend between beta carotene and risk of pre-invasive disease which is of borderline significance. These data have also been used to investigate the effects of smoking and oral contraceptive usage on the serum levels of retinol and beta carotene. Both habits tend to increase retinol and decrease beta carotene concentrations.. Women with invasive cancer of the cervix or with preinvasive disease and a control group of women with various benign gynecological problems were interviewed over the 1975-79 period at 2 hospitals and a health center in Oxfordshire, England, as part of a study designed to examine the hypothesis that the etiology of epithelial cancers might be related to a relative deficiency of dietary vitamin A. A sexual, obstetric, and contraceptive history was obtained from each woman. Blood samples were taken at the time of the interview from most of the study participants. Serum samples from 43 women with dysplasia, 38 women with carcinoma-in-situ, 32 women with invasive cancer, and 226 control women (matched for 5-year age group) were used. Serum samples were assayed for retinol and Beta-carotene. Analysis was carried out between 6-9 years after collection and initial freezing. Relative risks were computed for quintiles of serum levels of vitamin A and Beta-carotene as determined by the distributions among the controls, I being the lowest group and V the highest. The mean levels of serum retinol were similar in cases of all the disease categories and in cases and controls after full adjustment. This was the case for mean levels of serum Beta-carotene when comparing invasive cancer cases with controls. For both the preinvasive disease categories, the levels of Beta-carotene were lower among the cases than the controls at a significant level for the carcinoma-in-situ category and for both the preinvasive categories combined after full adjustment. No significant elevations, reductions, or trends in the odds ratios were found with retinol or Beta-carotene in any disease group. In the carcinoma-in-situ group, the odds ratio was greater than 4 in the 3 lowest Beta-carotene quintiles and of borderline significance. The comparison of the lowest 4 quintiles for the carcinoma-in-situ group with the highest gave an odds ratio of 4.0, a ratio of borderline significance. When the 2 preinvasive disease categories were combined, an elevated odds ratio of borderline significance was found for 2 of the 3 lower quintiles for the 4 low quintiles combined. Both smoking and OC use were independently associated with the serum measures; both habits tended to be linked with relatively high retinol and low Beta-carotene levels, respectively. The effect of smoking on Beta-carotene was quite strong. The results were similar in premenopausal and postmenopausal women. In sum, t

Topics: beta Carotene; Carcinoma in Situ; Carotenoids; Contraceptives, Oral; Female; Humans; Neoplasm Invasiveness; Smoking; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms; Vitamin A

This study of 513 white cervical cancer patients and 490 white hospitalized controls considered, with adjustment for marital history and parity, the effects of smoking and dietary characteristics on the relative risk of developing cervical cancer. Although smoking was shown to be positively associated with risk, no dose-response relationship was evident. The frequency of consumption of cruciferous vegetables was positively associated with risk. Respondent reports of the frequency of prior ingestion of several food items were used in constructing crude indices of exposure to basic nutrients; the index of beta-carotene exposure was negatively associated with risk, whereas the index of fat consumption was positively associated with risk.

Topics: Alcohol Drinking; beta Carotene; Carotenoids; Diet; Dietary Fats; Female; Humans; Meat; Risk; Smoking; Uterine Cervical Neoplasms; Vegetables; Vitamin A

Women with abnormal cytology were matched with normal control subjects for age, parity, ethnicity, and socioeconomic class and participated in a blind case-control study focused on the role of nutrition in cervical dysplasia. Sucrose gradient ultracentrifugation studies for determination of the presence and concentration of the binding proteins for retinol and retinoic acid were performed on colposcopic biopsy tissue specimens. The nutritional survey revealed statistically significant differences for vitamins A and C and beta carotene. Retinol binding protein was absent or minimally detectable and inversely related to the severity of the dysplasia. It is proposed that a double-blind clinical trial be conducted to evaluate whether retinoids may pharmacologically inhibit, arrest, or reverse cervical dysplasia.

Topics: Ascorbic Acid; beta Carotene; Carcinoma in Situ; Carotenoids; Diet; Female; Humans; Retinol-Binding Proteins; Tretinoin; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms; Vitamin A